Prevalence of and risk factors for microscopic and submicroscopic malaria infections in pregnancy: a systematic review and meta-analysis
Authors: Anna Maria van Eijk, Kasia Stepniewska, Jenny Hill, Steve M Taylor, Stephen J Rogerson, Gilles Cottrell, R Matthew Chico, Julie R Gutman, Halidou Tinto, Holger W Unger, Stephanie K Yanow, Steven R Meshnick, Feiko O ter Kuile, Alfredo Mayor, Anna Maria van Eijk, Kasia Stepniewska, Jenny Hill, Steve M. Taylor, Stephen J. Rogerson, Gilles Cottrell, R. Matthew Chico, Julie R. Gutman, Hallidou Tinto, Holger W. Unger, Stephanie K. Yanow, Manfred Accrombessi, Ayola A. Adegnika, Rukhsana Ahmed, Eliana María Arango-Flórez, Myriam Arevalo-Herrera, Emmanual Arinaitwe, Paulo Arnaldo, Per Ashorn, Ulla Ashorn, Azucena Bardaji, Inoni Betuela, Praveen K. Bharti, Francis Bohissou, Camila Bôtto-Menezes, Vera Braun, Valerie Briand, Jessica Briggs, María Eugenia Castellanos, Daniel Chandramohan, Enesia Banda Chaponda, Chetan Chitnis, Lauren M. Cohee, Michel Cot, Umberto d'Alessandro, Lise Denoeud-Ndam, Meghna Desai, Alassane Dicko, Xavier Ding, Grant Dorsey, Patrick E. Duffy, Maha A. Elbadry, Sonia M. Enosse, Yue Fan, Nadine Fievet, Michal Fried, Blaise Genton, Raquel Gonzalez, Brian Greenwood, Linda Kalilani, Johanna H. Kattenberg, Kassoum Kayentao, Carole Khairallah, Christopher L. King, Dhanpat Kumar Kochar, Swati Kochar, Felix Koukouikila-Koussounda, Sarah H. Landis, Miriam K. Laufer, Rose F. Leke, Eusebio Macete, Sonia Maculuve, Mwayiwawo Madanitsa, Almahamoudou Mahamar, Ken Maleta, Indu Malhotra, Rella Zoleko Manego, Flor Ernestina Martinez-Espinosa, Achille Massougbodji, Don Mathanga, Michela Menegon, Clara Menendez, Petra Mens, Martin Meremikwu, Frank P. Mockenhaupt, Ghyslain Mombo-Ngoma, Dominic Mosha, Ivo Mueller, Alain Nahum, Paul Natureeba, Nicaise Ndam, Francine Ntoumi, Olabisi A. Oduwole, Bernard A. Okech, Maria Ome-Kaius, Kephas Otieno, Norma Padilla, Michal Ramharter, Rosemary Rochford, Anna Rosanas-Urgell, Maria Ruperez, Katherine R. Sabourin, Sergi Sanz, Henk D. Schallig, Susana Scott, Esperanca Sevene, Carlo Severini, Harry Tagbor, Diane Wallace Taylor, Maminata Traore Coulibaly, Ana Vasquez, Annie Walker-Abbey, Blair J. Wylie, Djimon M. Zannou, Stephen R. Meshnick, Feiko O. ter Kuile, Alfredo Mayor
Journal: The Lancet Global Health (2023)

BackgroundMalaria infections during pregnancy can cause adverse birth outcomes, yet many infections are undetected by microscopy. We aimed to describe the epidemiology of submicroscopic malaria infections in pregnant women in Asia, the Americas, and Africa using aggregated and individual participant data (IPD).MethodsFor this systematic review and meta-analysis, studies (published Jan 1, 1997 to Nov 10, 2021) with information on both microscopic and submicroscopic infections during pregnancy from Asia, the Americas, or Africa, identified in the Malaria-in-Pregnancy Library, were eligible. Studies (or subgroups or study groups) that selected participants on the basis of the presence of fever or a positive blood smear were excluded to avoid selection bias. We obtained IPD (when available) and aggregated data. Estimates of malaria transmission intensity and sulfadoxine–pyrimethamine resistance, matched by study location and year, were obtained using publicly available data. One-stage multivariable logit and multinomial models with random intercepts for study site were used in meta-analysis to assess prevalence of and risk factors for submicroscopic infections during pregnancy and at delivery. This study is registered with PROSPERO, number CRD42015027342.FindingsThe search identified 87 eligible studies, 68 (78%) of which contributed to the analyses. Of these 68 studies, 45 (66%) studies contributed IPD (48 869 participants) and 23 (34%) studies contributed aggregated data (11 863 participants). During pregnancy, median prevalence estimates were 13·5% (range 0·0–55·9, 66 substudies) for submicroscopic and 8·0% (0·0–50·6, 66 substudies) for microscopic malaria. Among women with positive Plasmodium nucleic acid amplification tests (NAATs), the median proportion of submicroscopic infections was 58·7% (range 0·0–100); this proportion was highest in the Americas (73·3%, 0·0–100), followed by Asia (67·2%, 36·4–100) and Africa (56·5%, 20·5–97·7). In individual patient data analysis, compared with women with no malaria infections, those with submicroscopic infections were more likely to present with fever in Africa (adjusted odds ratio 1·32, 95% CI 1·02–1·72; p=0·038) but not in other regions. Among women with NAAT-positive infections in Asia and the Americas, Plasmodium vivax infections were more likely to be submicroscopic than Plasmodium falciparum infections (3·69, 2·45–5·54; p<0·0001). Risk factors for submicroscopic infections among women with NAAT-positive infections in Africa included older age (age ≥30 years), multigravidity, and no HIV infection.InterpretationDuring pregnancy, submicroscopic infections are more common than microscopic infections and are associated with fever in Africa. Malaria control in pregnancy should target both microscopic and submicroscopic infections.FundingBill & Melinda Gates Foundation through the Worldwide Antimalarial Resistance Network.